反应详情

温度

0 °C

4′-Bromo-2,2,2-trifluoracetophenone (1.80 mL, 11.9 mmol) was dissolved in tetrahydrofuran (60 mL), cooled to 0° C., and methylmagnesium bromide (19.8 mL, 59.3 mmol) was added. The reaction mixture was maintained at 0° C. for 1 hour and then allowed to warm to ambient temperature overnight. The reaction was quenched with saturated aqueous ammonium chloride and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous MgSO4, filtered, concentrated in vacuo and the crude residue was purified directly by MPLC on silica gel (using a gradient elution of 0-25% ethyl acetate in hexanes to afford a racemic mixture of the title compound. The mixture was resolved to the constituent enantiomers by Chiral SFC purification (Chiral Technology AZ-H 2.1×25 cm, 5 uM column; mobile phase: 5% methanol/CO2) to afford the title compounds as single enantiomers. Intermediate #11-1: First enantiomer to elute; (S or R)-2-(4-Bromophenyl)-1,1,1-trifluoropropan-2-ol; 1H NMR (500 MHz, CDCl3) δ 7.53-7.52 (d, 2H), 7.46-7.45 (d, 2H), 2.64 (bs, 1H), 1.76 (s, 3H). Intermediate #11-2: Second enantiomer to elute; (S or R)-2-(4-Bromophenyl)-1,1,1-trifluoropropan-2-ol; 1H NMR (500 MHz, CDCl3) δ 7.53-7.52 (d, 2H), 7.46-7.45 (d, 2H), 2.64 (bs, 1H), 1.76 (s, 3H).

1. temperatureThe reaction mixture was maintained at 0° C. for 1 hour
2. temperatureto warm to ambient temperature overnight
3. customThe reaction was quenched with saturated aqueous ammonium chloride
4. extractionextracted with ethyl acetate
5. washThe organic layer was washed with brine
6. dry with materialdried over anhydrous MgSO4
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customthe crude residue was purified directly by MPLC on silica gel (
10. washa gradient elution of 0-25% ethyl acetate in hexanes
11. customto afford